Mouse hepatitis virus (MHV) type 4 (JHM), a coronavirus, produces either an acute fatal encephalomyelitis or a chronic demyelinating disease. However, little is known about the mechanisms involved in a virus' potential to cause acute vs. chronic disease. Therefore, the overall objective of this proposed work is to determine the virus-dependent and the host-dependent factors affecting virus chronicity and persistence. Temperature-demyelination and chronic disease, as well as to elucidate the biological properties of this virus. Other virus variants including defective interfering virus and plaque variants will be isolated, and their disease-causing potentials will be evaluated. Of the host-dependent factors to be studied, a possible relationship between H-2 type and susceptibility to acute vs. chronic disease will be evaluated. Other host factors that may affect the development of chronic disease include the role of antibody induced antigenic modulation, depletion of complement levels, susceptibility of macrophages to infection and the role of cellular immunity. Clarification of the mechanism of MHV-induced disease will significantly contribute towards an understanding of virus persistent and of the pathobiology of associated diseases.